scholarly journals TRAF-interacting Protein (TRIP): A Novel Component of the Tumor Necrosis Factor Receptor (TNFR)- and CD30-TRAF Signaling Complexes That Inhibits TRAF2-mediated NF-κB Activation

1997 ◽  
Vol 185 (7) ◽  
pp. 1275-1286 ◽  
Author(s):  
Soo Young Lee ◽  
Sang Yull Lee ◽  
Yongwon Choi
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Activation ◽  
Tumor Necrosis Factor Receptor ◽  
Interacting Protein ◽  
Signaling Complex ◽  
Wide Range ◽  
Tnfr Superfamily ◽  
Necrosis Factor

Through their interaction with the TNF receptor–associated factor (TRAF) family, members of the tumor necrosis factor receptor (TNFR) superfamily elicit a wide range of biological effects including differentiation, proliferation, activation, or cell death. We have identified and characterized a novel component of the receptor–TRAF signaling complex, designated TRIP (TRAF-interacting protein), which contains a RING finger motif and an extended coiled-coil domain. TRIP associates with the TNFR2 or CD30 signaling complex through its interaction with TRAF proteins. When associated, TRIP inhibits the TRAF2-mediated NF-κB activation that is required for cell activation and also for protection against apoptosis. Thus, TRIP acts as a receptor–proximal regulator that may influence signals responsible for cell activation/proliferation and cell death induced by members of the TNFR superfamily.

scholarly journals Les futures générations d’anticorps modulateurs des points de contrôle de la réponse immunitaire

2019 ◽  
Vol 35 (12) ◽  
pp. 966-974
Author(s):  
Nathalie Bonnefoy ◽  
Daniel Olive ◽  
Bernard Vanhove
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Programmed Cell Death ◽  
T Cell Activation ◽  
Tumor Necrosis ◽  
Cell Activation ◽  
Tumor Necrosis Factor Receptor ◽  
Système Immunitaire ◽  
Necrosis Factor

Les points de contrôle du système immunitaire sont des systèmes moléculaires qui complètent les processus déclenchés par la reconnaissance antigénique en contrôlant l’inhibition ou l’activation des lymphocytes et des cellules myéloïdes, notamment celle des lymphocytes T régulateurs (Treg), permettant ainsi de combiner réponses immunes et maintien de la tolérance au soi. En cancérologie, l’inhibition de points de contrôle inhibiteurs vise à amplifier les réponses immunitaires existantes dirigées contre les tumeurs. Parmi ces points de contrôle inhibiteurs, dont des antagonistes sont en utilisation clinique, se trouvent CTLA-4 (cytolytic T-lymphocyte-associated antigen 4 ou CD152), PD-1 (programmed cell death 1, ou CD279), PD-L1 (programmed cell death-ligand 1, ou CD274), LAG-3 (Lymphocyte-activation gene 3, ou CD223), TIM3 (T-cell immunoglobulin and mucin-domain containing-3), TIGIT (T cell immunoreceptor with Ig and ITIM domains), VISTA (V-domain Ig suppressor of T cell activation), ou B7/H3 (ou CD276). La stimulation de points de contrôle activateurs tels que les molécules de co-activation CD28, CD137 (aussi appelé 4-1BB), OX40 [aussi appelé tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], GITR (Glucocorticoid-induced tumor necrosis factor receptor family-related protein) ou CD40, est également testée en cancérologie, le plus souvent en combinaison avec un antagoniste de point de contrôle inhibiteur. Dans les maladies auto-immunes et inflammatoires, des antagonistes de points de contrôle activateurs (CD28, CD40) et des agonistes de points de contrôle inhibiteurs (LAG-3) sont également à l’essai. Dans cette revue, nous mettons l’accent sur certains modulateurs de points de contrôle pour lesquels le mécanisme d’action a été particulièrement étudié. Cette description ne pouvant être exhaustive, nous avons regroupé dans le Tableau I l’ensemble des anticorps monoclonaux (AcM) ou protéines recombinantes en usage clinique à notre connaissance, modulant l’action d’un point de contrôle du système immunitaire.

scholarly journals T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors.

1996 ◽  
Vol 183 (2) ◽  
pp. 669-674 ◽  
Author(s):  
S Y Lee ◽  
C G Park ◽  
Y Choi
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
T Cell Receptor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Receptor ◽  
Cytoplasmic Domain ◽  
Activated T Cells ◽  
Necrosis Factor

CD30 is a member of the tumor necrosis factor superfamily and a surface marker for Hodgkin's disease. Normal activated T cells and several virally transformed T or B cell lines also show CD30 expression. The interaction of CD30 with its ligand induces cell death or proliferation, depending on the cell type. In this report we characterize the signals mediated by the intracellular domain of CD30 and show that, in combination with signal(s) transduced by the T cell receptor, the multimerization of CD30 cytoplasmic domain induces Fas(CD95)-independent cell death in T cell hybridomas. Deletion analysis shows that the COOH-terminal 66 amino acids of CD30 are required to induce cell death. Using the yeast two-hybrid system, we have identified that the same region of CD30 interacts with tumor necrosis factor receptor-associated factor (TRAF)1 and TRAF2. These results indicate that TRAF1 and/or TRAF2 play an important role in cell death in addition to their previously identified roles in cell proliferation.

scholarly journals Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Trine B. Levring ◽  
Martin Kongsbak-Wismann ◽  
Anna K. O. Rode ◽  
Fatima A. H. Al-Jaberi ◽  
Daniel V. Lopez ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Glucose Uptake ◽  
Tumor Necrosis ◽  
Gradient Centrifugation ◽  
Tumor Necrosis Factor Receptor ◽  
Down Regulation ◽  
Interacting Protein ◽  
Human T Cells ◽  
Necrosis Factor

Abstract In addition to antigen-driven signals, T cells need co-stimulatory signals for robust activation. Several receptors, including members of the tumor necrosis factor receptor superfamily (TNFRSF), can deliver co-stimulatory signals to T cells. Thioredoxin interacting protein (TXNIP) is an important inhibitor of glucose uptake and cell proliferation, but it is unknown how TXNIP is regulated in T cells. The aim of this study was to determine expression levels and regulation of TXNIP in human T cells. We found that naïve T cells express high levels of TXNIP and that treatment of blood samples with TNF results in rapid down-regulation of TXNIP in the T cells. TNF-induced TXNIP down-regulation correlated with increased glucose uptake. Furthermore, we found that density gradient centrifugation (DGC) induced down-regulation of TXNIP. We demonstrate that DGC induced TNF production that paralleled the TXNIP down-regulation. Treatment of blood with toll-like receptor (TLR) ligands induced TNF production and TXNIP down-regulation, suggesting that damage-associated molecular patterns (DAMPs), such as endogenous TLR ligands, released during DGC play a role in DGC-induced TXNIP down-regulation. Finally, we demonstrate that TNF-induced TXNIP down-regulation is dependent on caspase activity and is caused by caspase-mediated cleavage of TXNIP.

scholarly journals Posttranscriptional Downregulation of c-IAP2 by the Ubiquitin Protein Ligase c-IAP1 In Vivo

2005 ◽  
Vol 25 (8) ◽  
pp. 3348-3356 ◽  
Author(s):  
Dietrich B. Conze ◽  
Lori Albert ◽  
David A. Ferrick ◽  
David V. Goeddel ◽  
Wen-Chen Yeh ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Homologous Gene ◽  
Necrosis Factor Alpha ◽  
Ubiquitin Protein Ligase ◽  
Signaling Complex ◽  
Subsequent Degradation ◽  
Necrosis Factor

ABSTRACT Inhibitor of apoptosis proteins (IAPs) c-IAP1 and c-IAP2 were identified as part of the tumor necrosis factor receptor 2 (TNFR2) signaling complex and have been implicated as intermediaries in tumor necrosis factor alpha signaling. Like all RING domain-containing IAPs, c-IAP1 and c-IAP2 have ubiquitin protein ligase (E3) activity. To explore the function of c-IAP1 in a physiologic setting, c-IAP1-deficient mice were generated by homologous gene recombination. These animals are viable and have no obvious sensitization to proapoptotic stimuli. Cells from c-IAP1−/− mice do, however, express markedly elevated levels of c-IAP2 protein in the absence of increased c-IAP2 mRNA. In contrast to reports implicating c-IAPs in the activation of NF-κB, resting and cytokine-induced NF-κB activation was not impaired in c-IAP1-deficient cells. Transient transfection studies with wild-type and E3-defective c-IAP1 revealed that c-IAP2 is a direct target for c-IAP1-mediated ubiquitination and subsequent degradation, which are potentiated by the adaptor function of TRAF2. Thus, the c-IAPs represent a pair of TNFR-associated ubiquitin protein ligases in which one regulates the expression of the other by a posttranscriptional and E3-dependent mechanism.

scholarly journals A Critical Role of the p75 Tumor Necrosis Factor Receptor (p75TNF-R) in Organ Inflammation Independent of  TNF, Lymphotoxin α, or the p55TNF-R

1998 ◽  
Vol 188 (7) ◽  
pp. 1343-1352 ◽  
Author(s):  
Eleni Douni ◽  
George Kollias
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Peripheral Blood Mononuclear ◽  
Enhanced Production ◽  
Wide Range ◽  
Lymphotoxin Α ◽  
Necrosis Factor

Despite overwhelming evidence that enhanced production of the p75 tumor necrosis factor receptor (p75TNF-R) accompanies development of specific human inflammatory pathologies such as multi-organ failure during sepsis, inflammatory liver disease, pancreatitis, respiratory distress syndrome, or AIDS, the function of this receptor remains poorly defined in vivo. We show here that at levels relevant to human disease, production of the human p75TNF-R in transgenic mice results in a severe inflammatory syndrome involving mainly the pancreas, liver, kidney, and lung, and characterized by constitutively increased NF-κB activity in the peripheral blood mononuclear cell compartment. This process is shown to evolve independently of the presence of TNF, lymphotoxin α, or the p55TNF-R, although coexpression of a human TNF transgene accelerated pathology. These results establish an independent role for enhanced p75TNF-R production in the pathogenesis of inflammatory disease and implicate the direct involvement of this receptor in a wide range of human inflammatory pathologies.

scholarly journals Alix and ALG-2 Are Involved in Tumor Necrosis Factor Receptor 1-induced Cell Death

2008 ◽  
Vol 283 (50) ◽  
pp. 34954-34965 ◽  
Author(s):  
Anne-Laure Mahul-Mellier ◽  
Flavie Strappazzon ◽  
Anne Petiot ◽  
Christine Chatellard-Causse ◽  
Sakina Torch ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor
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